T cell homeostasis is central to the ability of vertebrate organisms to mount an effective immune response. Lymphocyte precursors, originating from the bone marrow, home to the thymus, where negative and positive selection results in the production of CD4 or CD8 single positive T lymphocytes. From the thymus, single positive T lymphocytes seed the peripheral organs, where they cycle for prolonged times between the secondary lymphoid organs and the blood in a naïve state. Following infection, T cells become activated by dendritic cells within peripheral lymph nodes, which induces massive proliferation of so-called effector T cells. After the infection has been cleared, effector cells have to be eliminated in order to maintain peripheral T cell homeostasis.
The signals that are responsible for the selection, proliferation and survival of T cells rely on stimulation of the T cell receptor by major histocompatibility complex (MHC) molecules that are present on antigen presenting molecules. While in the thymus, positive selection selects those thymocytes recognizing self-MHC molecules, negative selection ensures the elimination of those T cells that strongly recognize self-peptides in the context of self-MHC. Together, these selection processes within the thymus ensure the generation of naïve, non-autoreactive T cells for population of peripheral organs.
Once in the periphery, however, T cells need to be maintained in a naïve state while retaining the capacity to rapidly respond to an infection. Also these processes are regulated through activation of T cell receptors, both for the induction of T cell proliferation following an infection as well as for maintaining the naïve T cell population. While the distinction between life and death of a T cell appears to be controlled by the type of interaction with MHC molecules (A. Singer, Curr Opin Immunol 2002, 14, 207-215, A. Lanzavecchia and F. Sallusto, Curr Opin Immunol 2002, 12, 92-98), the molecular components involved in this decision are largely unknown.
Coronin 1 is also termed P57 or TACO (for tryptophan aspartate containing coat protein (G. Ferrari et al., Cell 1999, 97, 435-447). Coronin 1 is an F-actin interacting protein that is transcribed in all cells of the haematopoeitic lineage. Coronin 1 is a member of the WD repeat family of coronin proteins that are widely expressed in the eukaryotic kingdom (E. L. de Hostos, Trends Cell Biol 1999, 9, 345-350; J. Gatfield et al., Mol Biol Cell 2005, 16, 2786-2798). Whereas in Dictyostelium, which contains a single coronin gene, coronin is involved in actin-dependent processes such as phagocytosis, cell migration and cytokinesis (E. L. de Hostos et al., EMBO J 1991, 10, 4097-4104; M. Maniak et al., Cell 1995, 83, 915-924), in mammalian cells no biological activity has been assigned to any of the coronin homologues.
Mycobacterium spp. are highly successful pathogens that evade innate immunity by manipulating the host to ensure long term survival. A role of TACO (Coronin 1) was suggested for mycobacteria survival within macrophage phagosomes (G. Ferrari et al., loc. cit.).